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1.  Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1 
BMC Neurology  2013;13:131.
Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders causing learning disabilities by mutations in the neurofibromin gene, an important inhibitor of the RAS pathway. In a mouse model of NF1, a loss of function mutation of the neurofibromin gene resulted in increased gamma aminobutyric acid (GABA)-mediated inhibition which led to decreased synaptic plasticity and deficits in attentional performance. Most importantly, these defictis were normalized by lovastatin. This placebo-controlled, double blind, randomized study aimed to investigate synaptic plasticity and cognition in humans with NF1 and tried to answer the question whether potential deficits may be rescued by lovastatin.
In NF1 patients (n = 11; 19–44 years) and healthy controls (HC; n = 11; 19–31 years) paired pulse transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (paired pulse) and synaptic plasticity (paired associative stimulation). On behavioural level the Test of Attentional Performance (TAP) was used. To study the effect of 200 mg lovastatin for 4 days on all these parameters, a placebo-controlled, double blind, randomized trial was performed.
In patients with NF1, lovastatin revealed significant decrease of intracortical inhibition, significant increase of synaptic plasticity as well as significant increase of phasic alertness. Compared to HC, patients with NF1 exposed increased intracortical inhibition, impaired synaptic plasticity and deficits in phasic alertness.
This study demonstrates, for the first time, a link between a pathological RAS pathway activity, intracortical inhibition and impaired synaptic plasticity and its rescue by lovastatin in humans. Our findings revealed mechanisms of attention disorders in humans with NF1 and support the idea of a potential clinical benefit of lovastatin as a therapeutic option.
PMCID: PMC4015838  PMID: 24088225
Transcranial magnetic stimulation (TMS); Paired associative stimulation (PAS); Long-term potentiation (LTP); Synaptic plasticity; RAS-pathway; Developmental disorder; NF1; Attention; Lovastatin
3.  Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics? 
BMC Neurology  2011;11:43.
Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.
In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.
As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy.
Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.
PMCID: PMC3080296  PMID: 21453539
analgesics; fixed-dose combinations; headache; multi-target therapeutics; migraine; over-the-counter (OTC); pain; side effects; tension-type headache
4.  Diagnostic indices for vertiginous diseases 
BMC Neurology  2010;10:98.
Vertigo and dizziness are symptoms which are reported frequently in clinical practice. We aimed to develop diagnostic indices for four prevalent vertiginous diseases: benign paroxysmal positional vertigo (BPPV), Menière's disease (MD), vestibular migraine (VM), and phobic postural vertigo (PPV).
Based on a detailed questionnaire handed out to consecutive patients presenting for the first time in our dizziness clinic we preselected a set of seven questions with desirable diagnostic properties when compared with the final diagnosis after medical workup. Using exact logistic regression analysis diagnostic scores, each comprising of four to six items that can simply be added up, were built for each of the four diagnoses.
Of 193 patients 131 questionnaires were left after excluding those with missing consent or data. Applying the suggested cut-off points, sensitivity and specificity were 87.5 and 93.5% for BPPV, 100 and 87.4% for MD, 92.3 and 83.7% for VM, 73.7 and 84.1% for PPV, respectively. By changing the cut-off points sensitivity and specificity can be adjusted to meet diagnostic needs.
The diagnostic indices showed promising diagnostic properties. Once further validated, they could provide an ease to use and yet flexible tool for screening vertigo in clinical practice and epidemiological research.
PMCID: PMC2987857  PMID: 20973968
5.  The association between use of electronic media and prevalence of headache in adolescents: results from a population-based cross-sectional study 
BMC Neurology  2010;10:12.
Use of electronic media, i.e. mobile phones, computers, television, game consoles or listening to music, is very common, especially amongst adolescents. There is currently a debate about whether frequent use of these media might have adverse effects on health, especially on headaches, which are among the most-reported health complaints in adolescents. The aim of the present study was to assess associations between frequent use of electronic media and the prevalence of different types of headache in adolescents.
Data were derived from a population-based sample (n = 1,025, ages 13-17 years). Type of headache (i.e. migraine, tension-type headache, unclassifiable headache) was ascertained by standardized questionnaires for subjects reporting headache episodes at least once per month during the last six months. Duration of electronic media use was assessed during personal interviews. Associations were estimated with logistic regression models adjusted for age group, sex, family condition and socio-economic status.
Most of the adolescents used computers (85%), watched television (90%) or listened to music (90%) daily, otherwise only 23% of the participants used their mobile phones and only 25% played with game consoles on a daily basis. A statistically significant association between listening to music and any headache (odds ratio 1.8; 95% confidence interval 1.1-3.1 for 30 minutes per day, 2.1; 1.2-3.7 for 1 to 2 hours per day; 2.0; 1.2-3.5 for 3 hours and longer listening to music per day) was observed. When stratifying for type of headache, no statistically significant association was seen.
Apart from an association between listening to music on a daily basis and overall headache, no consistent associations between the use of electronic media and different types of headache were observed.
PMCID: PMC2834664  PMID: 20144204
6.  Co-morbidities of vertiginous diseases 
BMC Neurology  2009;9:29.
Co-morbidities of vertiginous diseases have so far not been investigated systematically. Thus, it is still unclear whether the different vertigo syndromes (e.g. benign paroxysmal positional vertigo (BPPV), Meniere's disease (MD), vestibular migraine and phobic vertigo (PPV)) have also different spectrums of co-morbidities.
All patients from a cohort of 131 participants were surveyed using a standardised questionnaire about the co-morbidities hypertension, diabetes mellitus, BMI (body mass index), migraine, other headache, and psychiatric diseases in general and the likelihood of a depression in particular.
We noted hypertension in 29.0% of the cohort, diabetes mellitus in 6.1%, migraine in 8.4%, other headache in 32.1%, psychiatric diseases in 16.0%, overweight and obesity in 33.6% and 13.7% respectively, as well as a clinical indication for depression in 15.9%.
In general, we did not detect an increased prevalence of the co-morbidities diabetes mellitus, arterial hypertension, migraine, other headache and obesity compared to the general population. There was an increased prevalence of psychiatric co-morbidity in patients with PPV, and the prevalence of hypertension was elevated in patients with MD.
PMCID: PMC2713979  PMID: 19583869

Results 1-6 (6)